The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 5 , Issue Supplement
Showing 1-5 articles out of 5 articles from the selected issue
  • Hirofumi MORIYUKI, Masamichi ICHIMURA
    1980 Volume 5 Issue Supplement Pages 1-9
    Published: December 25, 1980
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A new anti-tumor polysaccharide, lentinan (β-1, 3 Glucan) was studied on the acute toxicities using both sexes of mice (ICR) and rats (CD) treated by intravenously (i.v.), intraperitoneally (i.p.), subcutaneously (s.c.) and orally (p.o.). LD50 values in mg/kg body weight were essentially the same regardless of species as well as sexes and estimated a; follows : 250-500 (i.v.), >2500 (i.p., s.c., and p.o.). Cyanosis, convulsion and death were observed in both species of animals administered (i.v.) with only higher dosages of lentinan. No remarkable toxic signs being specific from lentinan were observed in any cases of treatment, i.p., s.c. and p.o. Gross findings : enlargement of the spleen (i.v.; i.p., s.c.) and coarse nodular surface of the kidneys (i.v.) in the both species of animals, erythema of the ears (i.v., i.p., s.c.) in mice, petechial hemorrhage of the lung and abdomen (i.v.), enlargement of the mesentric lymphonodes (i.v.) and edema of the diaphragm and intestine (i.p.) in rats were observed. In parallel, another sample of lentinan for clinical use prepared by freeze-dried procedure was tested in both sexes of mice and rats treated by i.v. alone, comparing with a original sample mentioned above. So far as the acute toxicities of lentinans concerned, no significant differences between two preparations were observed.
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  • Hiroyuki ISHII, Shuji USAMI, Tsumoru FUJIMOTO, Hirofumi MORIYUKI, Shig ...
    1980 Volume 5 Issue Supplement Pages 11-31
    Published: December 25, 1980
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Male and female JCL:SD rats were treated intravenously with lentinan in 5% mannitol solusion at dose levels of 0, 0.03, 3.0 and 30.0 mg/kg/day for 5 weeks. Rats receiving 0.3, 3.0 and 30.0 mg/kg/day showed reddening in ear, tail and scrotum and edema in legs and scrotum after day 3 of treatment. Males receiving 30.0 mg/kg/day gained less body weight than control. Occult blood was found in the urine of rats receiving 30.0 mg/kg/day. With regard to haematology, rats from the treatment groups had low mean values relating to red blood cell count, packed cell volume and haemoglobin, while high white blood cell count were recorded for these rats. Biochemical examinations revealed decreases in albumin level and A/G ratio and increases in β-globulin and γ-globulin levels for rats from the treatment groups. Slightly high values of BUN were showed for rats receiving 30.0 mg/kg/day. Organ weight analysis showed dose-dependent increase in the spleen, liver and adrenal. Histopathological changes attributable to treatment included (1) changes in reticuloendothelial system such as proliferation of reticular cells and micronodule of epithelioid cells in the spleen, liver and lymph nodes; (2) arteritis in many organs especially notable in epididymis, intestines and mesentery ;(3) haemorrhagic changes in lung, intestines and urinary bladder and secondary changes such as increased chronic nephropathy, hypospermatogenesis, spermatic granuloma in epididymis and granulomatous inflammation in ear, tail and scrotum. The maximum safe dose was estimated to be smaller than 0.03 mg/kg/day for males and 0.03 mg/kg/day for females in the present study.
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  • Hajime SHIMAZU, Kyoichi TAKEDA, Chiaki ONODERA, Ichiro MAKITA, Takashi ...
    1980 Volume 5 Issue Supplement Pages 33-57
    Published: December 25, 1980
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Chronic toxicity of lentinan was studied in male and female JCL:SD rats. Lentinan was given intravenously into tail vein. Dosage levels employed were 0 (5% mannitol), 0.01, 0.1, 1 (with or without dextran), and 10 mg/kg/day for 6 months in a volume of 1 ml/100 g body weight. After 6 months, the treatment was discontinued and a recovery study was performed for 3 months. Rats receiving 10 mg/kg had redness and necrosis of the tail, the treatment was stopped at week 5, and the rats were sacrificed. Rats receiving 1 mg/kg showed redness of the ear, tail, and scrotum, which was remarkable in the 2nd and 3rd months. Body weight gains were not adversely affected. Laboratory examinations revealed an increase in leukocyte count, decreases in differential eosinophile count and platelet count, and an increase in serum β-globilin level in drug-treated rats. At autopsy after 6 months, rats from the drug-treated groups had pulmonary hemorrhage and enlargements of the spleen and mesenteric lymph nodes. Histologic changes attributable to treatment included (1) activation of reticulo-endthelial system such as small epithelioid cell nodule in the liver, spleen, and mesenteric lymph nodes, and mobilization of Kupffer cells; (2) arteritis in various organs, especially notable in the spleen, testis, and epididymis ; (3) hemorrhage in the lung ; and (4) hypospermatogenesis. All these changes described above had a propensity to recover. The maximum no effect level was estimated to be less than 0.01 mg/kg in the present study in male and female rats.
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  • Yuichi OHARA
    1980 Volume 5 Issue Supplement Pages 59-72
    Published: December 25, 1980
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Fate of lentinan, which is one of antitumor polysaccharides, was investigated with 3H-lentinan. 3H-Ientinan was prepared by Wilzbach 3H gas exposure labeling, then purified by the gel filtration chromatography. 1) After a single intravenous injection of 3H-lentinan, radioactivity in plasma declined in a biphasic process. 2) There were urinary and fecal excretion, but expiratory excretion was a small proportion. 3) The radioactivity was predominantly incoporated into the liver and spleen, indicating selective retention of the lentinan in reticuloendthelial system cells. On the other hand the level of radioactivity in the lung and kidney was dropped rapidly. 4) We can not find the selective incorporation of radioactivity into the tumor. 5) There was no species difference on the distribution of lentinan among mouse, rat and dog. 6) These results obtained were similar to other polysaccharides and immunologic antitumor agents.
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  • Yuichi O'HARA
    1980 Volume 5 Issue Supplement Pages 73-80
    Published: December 25, 1980
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    ^3H-labeled lentinan was prepared by methylation with 3H-dimethyl-sulfate. Blood level, distribution and excretion were studied in rats. After intravenous injection of [methyl-3H]-methyl lentinan, radioactivity rapidly disappeared from blood, lung and kindney, distributed mainly in liver, spleen and mesenteric lymph nodes. There was urinary excretion, but expiratiry excretion was a small proportion. In the case of multi-injection of [methyl-3H]-methyl lentinan distribution of radioactivity was similar to a single injection, but retention of 3H was less than a single injection. Bile excretion and transport to fetuses and milk were in mere trace amounts. No substantial difference was found between two types of the 3H-labeled lentinan in either the distribution or excretion.
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